By transplanting neuronal precursor cells into the brains of mice, researchers have managed to reverse the learning and memory deficits in mouse models of Alzheimer’s disease and thus restore normal cognitive function. The study not only not only suggests a novel way to investigate how learning and memory is affected by certain diseases, but also raises the possibility that cell replacement therapy could be used to treat Alzheimer’s in the future. The study has been published in The Journal of Neuroscience.
In order for the brain to function normally, there needs to be a balance between excitatory and inhibitory activity in neural networks. Too much excitation can damage cells and lead to cell death, whereas excess inhibition prevents the flow of information. This balance is disrupted in the brains of Alzheimer’s disease (AD) patients as inhibitory neurons in a region of the brain called the hippocampus become damaged and die, leading to learning and memory problems. Two factors that are known to heavily contribute to this are Apolipoprotein (apo) E4 and amyloid-β (Aβ).
The study of Alzheimer’s has been facilitated by mouse models of the disease which allow researchers to examine disease progression and potential treatment avenues, amongst other things. In order to investigate whether replacing the lost or damaged neurons can improve brain signaling and alleviate disease symptoms, scientists from the Gladstone Institutes and the University of California San Francisco transplanted progenitor inhibitory neurons into the hippocampus of aged mice expressing apoE4. These are early-stage cells that are capable of maturing into inhibitory neurons.
Using aged mice is important in the study of AD because it is more representative of the scenario in humans, since AD is a progressive disease that is predominantly diagnosed in those over the age of 65.
Unexpectedly, the grafted cells not only survived in the brains of the mice and matured into inhibitory neurons, but they also functionally integrated into the neuronal circuit, restoring learning and memory. Furthermore, when they used apoE4 mice which also had excess levels of Aβ in their brains, similar to the brains of AD patients, the cognitive deficits displayed by the mice were once again alleviated.
Interestingly, the procedure left Aβ levels unaltered in the brain, which implies that the improvements were not a result of amyloid reduction.
“This is the first time transplantation of inhibitory neuron progenitors has been used in aged Alzheimer’s disease models,” lead author Leslie Tong said in a news-release. “Working with older animals can be challenging from a technical standpoint, and it was amazing to see that the cells not only survived but affected activity and behavior.”
While the researchers are a long way from being able to translate this into a treatment for humans, it remains an important proof of concept study and suggests that one day cell replacement therapy may help AD patients.
Header image "Hausmaus," by Nils J, via Flickr, used in accordance with CC BY-NC-SA 2.0.